An antibody plays important roles in the biophylaxis by specifically binding to a target antigen. Recently, antibody drugs which utilize its specific binding properties against its antigen have been developed as a therapeutic medication for autoimmune diseases or intractable diseases such as cancers, and its utility has high appraisal. In response to the development needs in effective manufacturing techniques for monoclonal antibodies having high specificity and high affinity which become antibody drugs, the techniques for making antigen-specific monoclonal antibodies by using gene cloning methods from human and mouse antibody producing cells have being established in recent years. The methods mainly include the following three steps: (1) isolation of antibody producing cells from peripheral bloods and lymphatic tissues of an immunity formation animal; (2) cloning of immunoglobulin genes from the antibody producing cells; and (3) antibody production by introducing the immunoglobulin genes into host cells. In order to make monoclonal antibodies effectively by using this technique, first of all antibody producing cells must be isolated with high purity. B lymphocyte or its terminally differentiated ones, plasma cells and plasmablasts are generally used as the antibody producing cells.
Plasma cells and plasmablasts are the cells which are terminally differentiated from B lymphocyte and specialized in antibody production. Since somatic mutations of antibody genes and selection with antigen which is called as affinity maturation are executed in these cells, these cells are particularly useful for isolating antibodies having high binding activities. However, because plasma cells and plasmablasts are heterogeneous cell population by consisting of several subsets and those abundance ratio is less 0.1% in lymphatic tissues, its isolation with high purity is difficult. Now, in order to identify and isolate plasma cells or plasmablasts from peripheral blood or lymph node, several steps of positive/negative selection are necessary which employ a combination of antibodies against at least three kinds of cell surface markers (Non Patent Literature 1).